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   Abstract
  Introduction
  Case Report
  Discussion
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CASE REPORT
Year : 2011  |  Volume : 59  |  Issue : 6  |  Page : 887-890

Dual pathology of corticobasal degeneration and Parkinson's disease in a patient with clinical features of progressive supranuclear palsy


1 Department of Neurology, Nambour General Hospital, QLD, Australia
2 Department of Geriatrics, Nambour General Hospital, QLD, Australia
3 Department of Anatomical Pathology, Royal Brisbane and Women's Hospital, QLD, Australia

Date of Submission08-Jul-2011
Date of Decision03-Aug-2011
Date of Acceptance29-Sep-2011
Date of Web Publication2-Jan-2012

Correspondence Address:
Tomin Mooney
Department of Neurology, Level 2, Block 6, Nambour General Hospital, 33 Hospital Road, Nambour, QLD 4560
Australia
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DOI: 10.4103/0028-3886.91371

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  Abstract 

Corticobasal degeneration and Parkinson's disease are pathologically distinct disorders with unique histological and biochemical features of a tauopathy and a-synucleinopathy respectively. We report the first case of co-occurrence of these pathologies in the same patient. Convergence of such distinctly separate neuropathology in the same brain highlights the need for extensive brain banking and further research in supporting the hypothesis that tauopathies and a-synucleinopathies might share common pathogenic mechanisms.


Keywords: Concurrent pathology, corticobasal degeneration, multiple system atrophy, Parkinson′s disease, progressive supra nuclear palsy, synucleinopathy, tauopathy


How to cite this article:
Mooney T, Tampiyappa A, Robertson T, Grimley R, Burke C, Ng K, Patrikios P. Dual pathology of corticobasal degeneration and Parkinson's disease in a patient with clinical features of progressive supranuclear palsy. Neurol India 2011;59:887-90

How to cite this URL:
Mooney T, Tampiyappa A, Robertson T, Grimley R, Burke C, Ng K, Patrikios P. Dual pathology of corticobasal degeneration and Parkinson's disease in a patient with clinical features of progressive supranuclear palsy. Neurol India [serial online] 2011 [cited 2014 Jul 22];59:887-90. Available from: http://www.neurologyindia.com/text.asp?2011/59/6/887/91371



  Introduction Top


Concomitant pathology of progressive supranuclear palsy (PSP) type tauopathy and multiple system atrophy (MSA) type synucleinopathy in the same patient has been previously reported. [1] Corticobasal degeneration (CBD) and Parkinson's disease (PD) are pathologically distinct disorders with unique histological and biochemical features of a tauopathy and a-synucleinopathy respectively. We report the first case of co-occurrence of these pathologies in the same patient.


  Case Report Top


A 55 year-old right-handed male presented with a three year history of a progressive rigid akinetic syndrome. After a two year prodrome of myalgia, increasing fatigue and depression he developed facial hypomimia, symmetric limb rigidity, bradykinesia, stooped shuffling gait and occasional postural tremor of the hands without any rest tremor. There was no family history of similar complaints. After a six-month period of initial partial response the effect of L-Dopa declined and his symptoms progressed with motor fluctuations, wearing off and onset of dysphagia. Addition of entacapone did not alter the progression of symptoms.

Twenty four months from onset he was wheelchair bound with marked gait impairment and multiple falls. Vertical eye movements showed a supranuclear gaze palsy that was more marked in down gaze. Moderate dysphagia necessitated diet modifications and dysarthria with dysphonia affected verbal communication. Significant cervical rigidity with antero and laterocollis was also evident. Tremors, myoclonus and limb dystonias were absent and praxis was intact. Although frontal lobe release reflexes were present there were no pyramidal tract signs and the primary and cortical sensations were intact. His family had noticed some memory impairment but here was no urinary incontinence or postural hypotension.

Thirty-six months from onset he was admitted with marked decline in function including severely restricted overall mobility, dysphagia and episodic drenching whole-body sweats. The latter responded to cessation of the L-dopa and was thought to be medication-related. Clinically, in addition to profound axial as well as appendicular rigidity, bradykinesia, cervical dystonia and bulbar dysfunction, there was restriction of all extraocular movements and an apraxia of eyelid opening. He scored 19/30 in the Folstein Mini Mental Score and detailed cognitive assessment showed additional severe deficits in attention, orientation and constructional abilities. Computed tomography (CT) and magnetic resonance imaging (MRI) brain revealed mild age-related atrophy without any regional predisposition. A diagnosis of probable progressive supranuclear palsy was made and despite supportive measures he succumbed to hospital-acquired pneumonia.

Post-mortem brain examination showed mild fronto-parietal atrophy and pallor of substantia nigra and subthalamic nucleus macroscopically [Figure 1]. Microscopic examination revealed moderate neuronal loss, spongiosis and gliosis in the frontal lobe and to a lesser extent in the temporal and parietal lobes. Scattered balloon cells were present in the frontal cortex [Figure 2], [Figure 3] and [Figure 4]. The substantia nigra showed severe neuronal loss with gliosis and Lewy bodies [Figure 5]. Neuronal loss and Lewy bodies were also present in the locus ceruleus, dorsal nucleus of the vagus, amygdala and nucleus basalis. The remaining brainstem nuclei, cerebellum, basal ganglia, thalamus and subthalamic nucleus were relatively intact. Immunohistochemical stains revealed widespread tau deposition in the form of neuronal tangles and pretangles, frequent neuropil threads in the cortex and white matter, and frequent astrocytic plaques in the cortex [Figure 6] and [Figure 7]. Immunohistochemcial staining for beta-amyloid was negative. These changes met the neuropathological criteria for corticobasal degeneration. [2] The subthalamic nucleus and substantia nigra showed only mild tau deposition but there was prominent alpha synuclein immunoreactivity in Lewy bodies and neurites in the substantia nigra, amygdala and ventral pallidum in keeping with idiopathic Parkinson's disease [Figure 8]. No glial cytoplasmic inclusions were seen.
Figure 1: Gross pathology of brain

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Figure 2: Balloon (achromatic) neuron at centre showing cytoplasmic vacuolation and also weak peripheral immunoreactivity for tau in the cytoplasm

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Figure 3: Balloon (achromatic) neuron showing strong immunoreactivity for alpha-B crystalline

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Figure 4: Balloon neuron in the frontal cortex (H and E stain; original magnification, ×400)

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Figure 5: Substantia nigra showing a surviving neuron with a Lewy body (centre). There is evidence of neuronal loss with background free neuromelanin (H and E stain; original magnification, ×400)

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Figure 6: Tau immunohistochemistry showing an astrocytic plaque (left of centre) and tau-positive neurons (right of centre) with numerous background tau-positive neuropil threads in the frontal cortex (Original magnification, ×200)

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Figure 7: Gallyas silver stain showing an astrocytic plaque in the frontal cortex (Original magnification, ×400)

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Figure 8: Alpha-synuclein immunohistochemistry of the substantia nigra showing neuronal synuclein immunoreactivity and background Lewy neurites (Original magnification, ×400)

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  Discussion Top


The correlation between the antemortem clinical diagnoses of Parkinsonian syndromes with its neuropathology is often discordant. [3] Although there may be an overlap in their clinical features in the initial stages, CBD and PD are pathologically distinct in being a tauopathy and α-synucleinopathy respectively. CBD has traditionally been considered to be a distinct clinico-pathological entity presenting as a corticobasal syndrome with asymmetric apraxia, cortical sensory loss, alien limb phenomenon, myoclonus, rigidity and dystonia. [4] The pathological hallmark of this tauopathy is the presence of focal cortical neuronal loss with widespread tau-positive astrocytic plaques, glial and neuronal threads, cortical ballooned neurons and coiled bodies. [2] But recently a strong body of literature has emerged indicating that the pathological entity of CBD is associated with considerable heterogeneity in its clinical presentation including that of a frontotemporal dementia, progressive nonfluent aphasia and a progressive supranuclear palsy-like syndrome among others. [4] In our case the clinical presentation and progression resembled closely that of PSP, only for the neuropathology to prove it as CBD with concomitant idiopathic PD with characteristic Lewy body and other alpha synuclein positive inclusions distributed in the locus ceruleus, dorsal nucleus of the vagus, amygdala and substantia nigra.

Dual pathology with tauopathy and α-synucleinopathy is known to occur. Co-occurrence of an Alzheimer's disease type and PD type pathology is higher than would be expected by chance alone.[1] Silveira-Moriyama et al., reviewing the coexistence of a PSP type tauopathy with an MSA type synucleinopathy described four such cases and based on the prevalence of those two disorders suggested that the co-occurrence was more than mere coincidence. [1] PSP type tauopathy coexisting with a PD type synucleinopathy has also been reported. [5] But to the best of our knowledge this is the first instance of concurrent CBD type tauopathy and PD type synucleinopathy to be reported. With an incidence of less than 1 per 100,000 CBD is distinctly rarer than the more widely prevalent PD. Hence the unique dual pathology in our case could be a chance association. Despite this unique concurrent pathology the patient had clinical features of neither typical PD or CBD and resembled PSP most closely before death again illustrating the divergence of neuropathology from the clinical diagnosis seen in these syndromes. Whether the dual pathology contributed to the young age of onset and the markedly rapid progression is debatable. Convergence of such distinctly separate neuropathology in the same brain highlights the need for extensive brain banking and further research in supporting the hypothesis that tauopathies and α-synucleinopathies might share common pathogenic mechanisms.

 
  References Top

1.Silveira-Moriyama L, González AM, O'Sullivan SS, Williams DR, Massey L, Parkkinen L, et al. Concomitant progressive supranuclear palsy and multiple system atrophy: More than a simple twist of fate? Neurosci Lett 2009;467:208-11.  Back to cited text no. 1
    
2.Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, et al. Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 2002;61:935-46.  Back to cited text no. 2
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3.Hughes A, Daniel S, Ben-Shlomo Y, Lees A. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 2002;125:861-70.  Back to cited text no. 3
    
4.Wadia PM, Lang AE. The many faces of corticobasal degeneration. Parkinsonism Relat Disord 2007;13 (Suppl 3): S336-40.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.Judkins AR, Forman MS, Uryu K, Hinkle DA, Asbury AK, Lee VM, et al. Co-occurrence of Parkinson's disease with progressive supranuclear palsy. Acta Neuropathol 2002;103:526-30.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]

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